Mycophenolic Acid Trough Concentration and Dose Are Associated with Hematologic Abnormalities but Not Rejection in Kidney Transplant Recipients

J Korean Med Sci. 2020 Jun 22;35(24):e185. doi: 10.3346/jkms.2020.35.e185.

Abstract

Background: Little is known regarding the safe fixed dose of mycophenolic acid (MPA) for preventing biopsy-proven acute rejection (BPAR) in kidney transplant recipients (KTRs). We investigated the correlation of MPA trough concentration (MPA C₀) and dose with renal transplant outcomes and adverse events.

Methods: This study included 79 consecutive KTRs who received MPA with tacrolimus (TAC) and corticosteroids. The MPA C₀ of all the enrolled KTRs was measured, which was determined monthly by using particle-enhanced turbidimetric inhibition immunoassay for 12 months, and clinical data were collected at each time point. The clinical endpoints included BPAR, any cytopenia, and BK or cytomegalovirus infections.

Results: No differences in MPA C₀ and dose were observed between KTRs with or without BPAR or viral infections under statistically comparable TAC concentrations. MPA C₀ was significantly higher in patients with leukopenia (P = 0.021) and anemia (P = 0.002) compared with those without cytopenia. The MPA dose was significantly higher in patients with thrombocytopenia (P = 0.002) compared with those without thrombocytopenia. MPA C₀ ≥ 3.5 μg/mL was an independent risk factor for leukopenia (adjusted odds ratio [AOR], 3.80; 95% confidence interval [CI], 1.24-11.64; P = 0.019) and anemia (AOR, 5.90; 95% CI, 1.27-27.51; P = 0.024). An MPA dose greater than the mean value of 1,188.8 mg/day was an independent risk factor for thrombocytopenia (AOR, 3.83; 95% CI, 1.15-12.78; P = 0.029). However, an MPA dose less than the mean value of 1,137.3 mg/day did not increase the risk of BPAR.

Conclusion: Either a higher MPA C₀ or dose is associated with an increased risk of cytopenia, but neither a lower MPA C₀ nor dose is associated with BPAR within the first year of transplantation. Hence, a reduced MPA dose with TAC and corticosteroids might be safe in terms of reducing hematologic abnormalities without causing rejection.

Keywords: Dose; Drug Monitoring; Graft Rejection; Kidney Transplantation; Mycophenolic Acid.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Anemia / etiology
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Graft Rejection / etiology
  • Graft Rejection / prevention & control*
  • Hematologic Diseases / etiology*
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation / adverse effects*
  • Leukopenia / etiology
  • Logistic Models
  • Male
  • Middle Aged
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / therapeutic use*
  • Odds Ratio
  • Risk Factors
  • Tacrolimus / therapeutic use
  • Thrombocytopenia / etiology

Substances

  • Adrenal Cortex Hormones
  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Tacrolimus